In the context of the present invention a soft pastille means a resilient preparation which is can be retained and sucked in the mouth.
Nicotine is an alkaloid found in the plants belonging to family Solanaceae. Nicotine is a hygroscopic, oily liquid which is miscible with water in its base form. Nicotine is optically active and has two enantiomeric forms. The naturally occurring form of nicotine is levorotatory. The dextrorotatory form ((+) nicotine) has only one-half the physiological activity of (−) nicotine. It is therefore weaker in the sense that a higher dose is required to attain the same effects. As nicotine enters the body, it is distributed quickly through the bloodstream and can cross the blood-brain barrier. On an average it takes about ten seconds for the substance to reach the brain when inhaled. The half life of nicotine in the body is around two hours.
Nicotine is the main addictive ingredient in the tobacco used in cigarettes, cigars, snuff and other nicotine-containing products. It is generally known that active as well as passive smoking of tobacco products, such as cigarettes, cigars and pipe tobacco presents serious health risks to the user and those subjected to secondary smoke. It is also known that the use of smokeless forms of tobacco, such as chewing tobacco, spit tobacco and snuff tobacco presents serious health risk to the user.
During smoking a cigarette, nicotine is quickly absorbed into the smoker's blood and reaches the brain within ten seconds after inhalation. The quick uptake of nicotine gives the consumer a rapid satisfaction or kick. The poisonous, toxic, carcinogenic and addictive nature of smoking has initiated efforts to search for methods, compositions and devices which would help in breaking the habit of smoking cigarettes.
Smokers and other tobacco users often try to quit the potentially deadly habit. Although the damaging effects of tobacco usage are well known, most individuals who are nicotine dependent have great difficulty in overcoming their dependence on nicotine. The difficulty arises in part due to the highly addictive nature of nicotine and the strong nicotine withdrawal symptoms that can occur when one begins to deprive the body of the nicotine. Overcoming nicotine withdrawal symptoms is a critical challenge for those attempting to conquer nicotine dependence.
A wide variety of nicotine cessation products and therapies are known. However, in most of the cases the mere replacement of cigarettes with another nicotine source may not be sufficient to ensure success in smoking cessation therapy. The available nicotine cessation products include lozenges, gums, transdermal patches and the like. Lozenges and chewing gums provide oral delivery of nicotine, whereas transdermal patch treatments deliver nicotine through the wearer's skin.
Nicotine chewing gum containing nicotine polacrilex and transdermal nicotine are two of the more popular forms of nicotine replacement available commercially.
Nicotine gum is actually an ion-exchange resin that releases nicotine slowly when the patient chews and the nicotine present in the mouth is delivered directly to the systemic circulation by buccal absorption. However, much of the nicotine is retained in the gum through incomplete chewing or is largely wasted through swallowing, so that the systemic bioavailability of nicotine from gum is low and averages only 30-40%.
Furthermore, most commercially available products such as chewing gums, lozenges for nicotine replacement in smoking cessation therapy do not specifically address the issue of taste masking and side effects of nicotine ingestion such as nausea and burning sensation. Instead, they generally target providing a stable baseline level of nicotine in the blood.
The following patents/patent applications disclose compositions containing nicotine.
U.S. Pat. No. 4,967,773 discloses a lozenge formed by compression of at least two mixed components, one of said components including lactose or a lactose containing substance and the other of said components comprising a carrier having nicotine or a nicotine derivative absorbed therein such that there is no direct contact between the nicotine and the lactose whilst together in the lozenge.
GB2230439 discloses a lozenge which is a substitute for smoking tobacco comprises a lozenge core which contains nicotine and/or a nicotine substitute and a shell or coating around the lozenge core.
GB2299756 discloses pastilles containing nicotine in an acacia gum or gelatine base.
U.S. Pat. No. 5,488,962 discloses chewing gum formed into 3 g strips, characterized in that each strip contains not more than 25 wt. % of a gum base and from 0.3-0.4 mg of nicotine dispersed in the gum base.
U.S. Pat. No. 6,183,775 discloses a controlled release lozenge consisting of (a) 50 to 99% of a soluble filler; (b) 0.5 to 30% of an insoluble film forming agent which is selected from the group consisting of a polyacrylate, ethyl cellulose and mixtures thereof; (c) 0.5 to 30% of a swellable polymer which is selected from the group consisting of xanthan gum, guar gum, cellulose derivatives and mixtures thereof; and (d) nicotine or a salt or derivative of nicotine.
U.S. Pat. No. 6,280,761 discloses a nicotine lozenge consisting of nicotine, mannitol, xylitol, mint flavor, ammonium glycyrrhizinate, sodium carbonate, sodium bicarbonate, hydrogenated vegetable oil and magnesium stearate.
U.S. Pat. No. 6,344,222 discloses a chewing gum composition for systemic, oral administration of nicotine constituent, said composition comprising a) a nicotine constituent; b) a gum base matrix, said gum base matrix including at least one hydrophilic polymer and at least one hydrophobic polymer; and c) a buffer.
US2004151771 discloses a flavored a lozenge comprising a sustained release wet matrix of ethylcellulose and a flavoring agent selected from essential oils, constituents of essential oils, and mixtures thereof, wherein, in an aqueous environment, the matrix gradually releases the flavoring agent over a time period of at least 45 minutes. The active ingredient used is nicotine
US2005034738 discloses a chewing tobacco substitute comprising a non-tobacco leaf-like material; an alkaline chemical; and a nicotine compound capable of being absorbed orally. The nicotine compound used is nicotine polacrilex.
US2005002993 discloses a confectionery product for delivering at least one pharmaceutically active agent [such as nicotine replacement agents] which includes a hard outer shell and a core comprised of a core material which is or forms a liquid-like to a gel-like substance in the oral cavity and is capable of delivering pharmaceutically active agents to infected and/or irritated tissues of the throat.
US2005123502 discloses an oral composition comprising a nicotine active, a polycarbophil component or a salt thereof and an alginic acid component or a salt thereof.
US20050053665 discloses a nicotine-containing pharmaceutical composition comprising nicotine and cellulose of non-seed organism origin. Said composition can be in the form of chewing gum, mouth spray, buccal sachet, lozenge or a tablet.
US2007269492 discloses a coated oral dosage forms for the delivery of nicotine in any form to a subject by rapid intraoral delivery of nicotine comprising at least one core, nicotine in any form and/or a nicotine mimicking agent, at least one coating layer and optionally at least one additive.
US2007269386 discloses a buffered pharmaceutical oral formulation comprising nicotine, characterized in that it is buffered with at least trometamol. The formulation can be in the form of a mouth spray, a capsule, a chewing gum, a chewable tablet, a tablet, a melt tablet and a lozenge.
International Publication No. WO/2009/134947 discloses an oral lozenge composition comprising: a) a master granule component comprising: at least one an alkaline buffering agent; at least one dissolution modifier; and at least one filler; b) a nicotine polacrilex; and c) at least one alkaline buffering agent. The dissolution modifier used is selected from the group consisting of xanthan gum, acacia, carbomer, carboxymethylcellulose, carrageenan and cellulose.
US20100004294 discloses a lozenge composition for achievement of a fast onset of action of nicotine after application of the solid dosage form to the oral cavity of a subject, comprising a nicotine-cellulose combination and one or more pharmaceutically acceptable excipients.
Short comings and problems associated with the known nicotine containing compositions:                Nicotine containing products in the form of chewing gums are associated with problems such as disposal problem and chewing is very often socially unacceptable.        Further, much of the nicotine is retained in the gum through incomplete chewing or is largely wasted through swallowing which in turn results in low systemic bioavailability (about 30 to 40%).        Furthermore, chewing of chewing gum leads to breaking of polymer coating and result in excessive release of nicotine in buccal cavity which in turn causes nausea, bad taste and burning sensation.        Nicotine containing lozenges also possess disadvantages such as person using such lozenges is not comfortable to keep a hard product in the buccal cavity for prolong period. Another disadvantage is that lozenges get break down into pieces followed by accidental swallowing which in turn result in excessive transfer of nicotine in GI tract and causes nausea and burning sensation.        
Accordingly, it is desirable to develop a palatable nicotine containing formulation which is devoid of gums and which releases the nicotine for prolong period of time in controlled manner without causing nausea, bad taste and burning sensation.